Biography

Ph.D. UMass Medical School, 1995
B.S. UMass Amherst, 1989

Affiliations

Research Consultant/Visiting Investigator
The Jackson Laboratory, Bar Harbor, ME,
2002 – present.

Bone and Cartilage Cell Biology

Deeper knowledge of basic skeletal cell biology has long-range implications for understanding many pervasive clinical conditions, such as osteoporosis, osteoarthritis, and genetic conditions that affect bone growth. Our lab group studies how the cells of the skeleton function and how they communicate and regulate one another, with particular emphasis on the multinucleated, monocyte/macrophage-derived, bone-resorbing osteoclast. Lab website [http://www.umassmed.edu/cellbio/odgrenlab/index.aspx]

Our main approach has been to use rat and mouse models with genetic abnormalities that block osteoclast differentiation and/or activity, resulting in a condition called osteopetrosis. Osteopetrosis produces dense bones lacking marrow spaces, failure of teeth to erupt through the laws, lack of marrow spaces in the bones, and growth defects due to the failure to remove growth cartilage and to remodel growing bones. Through gene mapping and expression studies, we have identified novel effector genes which play critical roles in osteoclast biology. We have also applied advanced histopatholgical techniques to investigate the detailed impacts of gene function in the tissues, including upon angiogenesis and gene expression. We recently mapped the toothless and incisors absent (ia) mutations in the rat and in so doing discovered a novel gene which also causes osteopetrosis when mutated in humans. Efforts to map the final osteopetrotic mutation in a different rat strain are ongoing in the lab.

Work in the ia rat model has led to further investigations into the cell biology of the causative gene, called Plekhm1.The plekhm1 protein has a modular, multi-domain structure, suggesting multiple, regulated interactions. Vesicle trafficking and secretion are defective in ia rat osteoclasts, and the co-localization of plekhm1 with the small GTPase, rab7, is the starting point for collaborative investigations we have undertaken with colleagues in Antwerp, Aberdeen, and Frankfurt.

We have also used gene expression profiling in vivo and in vitro to discover genes which make critical contributions to osteoclast differentiation and activity. This work led to a series of recent papers in which we reported on the entire chemokine and receptor repertoire; the GTP-coupled receptor, OGR1; a novel cell surface receptor we called OC-STAMP; and, in collaboration with investigators at the Forsythe Institute for Dental Medicine in Boston, we have recently described novel mitochondrial and redox proteins.

Another ongoing collaboration is with investigators at The Jackson Laboratories in Bar Harbor, where we have been helping to investigate and characterize mutant strains of mice with craniofacial defects. A report describing the first naturally-occurring mutation in the lamin A/C gene and its impact on craniofacial and skeletal growth is currently in press.

Our lab continues the work of Sandy C. Marks, Jr., DDS, PhD, for more on Sandy, follow this link:
 http://www.umassmed.edu/cellbio/sandymarks.aspx

Download a memorial booklet comprised of contributions from colleagues, and friends worldwide. (PDF 2.3 MB)